Prognostic impact of TP53 mutation, monosomal karyotype, and prior myeloid disorder in nonremission acute myeloid leukemia at allo-HSCT.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
26
01
2020
accepted:
24
07
2020
revised:
09
07
2020
pubmed:
8
8
2020
medline:
22
6
2021
entrez:
8
8
2020
Statut:
ppublish
Résumé
Outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in nonremission acute myeloid leukemia (AML) are dismal [2-year overall survival (OS): 20-30%]. Though several risk classifications have been used, some factors are unavailable until the start of conditioning or transplantation. We analyzed prognostic gene mutations by targeted next-generation sequencing to identify predisposing factors for predicting OS at 1 month before transplantation. We enrolled 120 patients with nonremission AML who underwent first allo-HSCT between 2005 and 2018. Mutations were found in 98 patients; frequently mutated genes were FLT3-ITD, TP53, RUNX1, and WT1. TP53 mutation was detected in 21 patients and was the only predictor of poor OS. Multivariate analysis using Cox regression hazard model revealed primary AML, monosomal karyotype (MK), and TP53 mutation as independent factors for predicting poor OS. Based on these, patients were stratified into three groups. The low-risk group included patients with prior myeloid disorder without MK (n = 26). Among the rest, patients with TP53 mutation were assigned to the high-risk group (n = 19) and the rest into the intermediate-risk group (n = 75). Two-year OS in low-, intermediate-, and high-risk groups differed significantly (50.0%, 24.9%, and 0%, respectively). This suggests that the indication of allo-HSCT should be carefully judged for high-risk patients.
Identifiants
pubmed: 32760007
doi: 10.1038/s41409-020-01016-9
pii: 10.1038/s41409-020-01016-9
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
334-346Références
Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71.
pubmed: 24744269
pmcid: 4047501
doi: 10.1182/blood-2014-01-552984
Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28:3730–8.
pubmed: 20625136
pmcid: 2917308
doi: 10.1200/JCO.2010.28.8852
Nagler A, Savani BN, Labopin M, Polge E, Passweg J, Finke J, et al. Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. Lancet Haematol. 2015;2:e384–92.
doi: 10.1016/S2352-3026(15)00146-5
pubmed: 26685771
Gyurkocza B, Lazarus HM, Giralt S. Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission: potentially curative therapy. Bone Marrow Transplant. 2017;52:1083–90.
doi: 10.1038/bmt.2017.8
pubmed: 28244979
Tachibana T, Kanda J, Ishizaki T, Najima Y, Tanaka M, Doki N, et al. Prognostic index for patients with relapsed or refractory acute myeloid leukemia who underwent hematopoietic cell transplantation: a KSGCT multicenter analysis. Leukemia. 2019;33:2610–8.
doi: 10.1038/s41375-019-0494-9
pubmed: 31147621
Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017;376:536–47.
pubmed: 28177873
pmcid: 5438571
doi: 10.1056/NEJMoa1611604
Thol F, Gabdoulline R, Liebich A, Klement P, Schiller J, Kandziora C, et al. Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. Blood. 2018;132:1703–13.
pubmed: 30190321
doi: 10.1182/blood-2018-02-829911
Duncavage EJ, Jacoby MA, Chang GS, Miller CA, Edwin N, Shao J, et al. Mutation clearance after transplantation for myelodysplastic syndrome. N Engl J Med. 2018;379:1028–41.
pubmed: 30207916
pmcid: 6309244
doi: 10.1056/NEJMoa1804714
Wong HY, Sung AD, Lindblad KE, Sheela S, Roloff GW, Rizzieri D, et al. Molecular measurable residual disease testing of blood during AML cytotoxic therapy for early prediction of clinical response. Front Oncol. 2018;8:669.
doi: 10.3389/fonc.2018.00669
pubmed: 30697529
Breems DA, Van Putten WL, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KB, Mellink CH, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26:4791–7.
doi: 10.1200/JCO.2008.16.0259
pubmed: 18695255
Au CH, Wa A, Ho DN, Chan TL, Ma ES. Clinical evaluation of panel testing by next-generation sequencing (NGS) for gene mutations in myeloid neoplasms. Diagn Pathol. 2016;11:11.
pubmed: 26796102
pmcid: 4722624
doi: 10.1186/s13000-016-0456-8
O’Leary NA, Wright MW, Brister JR, Ciufo S, Haddad D, McVeigh R, et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 2016;44:D733–45.
doi: 10.1093/nar/gkv1189
pubmed: 26553804
Forbes SA, Beare D, Boutselakis H, Bamford S, Bindal N, Tate J, et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 2017;45:D777–83.
doi: 10.1093/nar/gkw1121
pubmed: 27899578
Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014;42:D980–5.
doi: 10.1093/nar/gkt1113
pubmed: 24234437
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–91.
pubmed: 27535533
pmcid: 5018207
doi: 10.1038/nature19057
Little RJ, Rubin DB. Causal effects in clinical and epidemiological studies via potential outcomes: concepts and analytical approaches. Annu Rev Public Health. 2000;21:121–45.
doi: 10.1146/annurev.publhealth.21.1.121
pubmed: 10884949
Cole SR, Hernan MA. Adjusted survival curves with inverse probability weights. Comput Methods Prog Biomed. 2004;75:45–49.
doi: 10.1016/j.cmpb.2003.10.004
Konuma T, Harada K, Yamasaki S, Mizuno S, Uchida N, Takahashi S, et al. Upfront allogeneic hematopoietic cell transplantation (HCT) versus remission induction chemotherapy followed by allogeneic HCT for acute myeloid leukemia with multilineage dysplasia: a propensity score matched analysis. Am J Hematol. 2019;94:103–10.
doi: 10.1002/ajh.25336
pubmed: 30370944
Fuji S, Yamaguchi T, Inoue Y, Utsunomiya A, Moriuchi Y, Owatari S, et al. VCAP-AMP-VECP as a preferable induction chemotherapy in transplant-eligible patients with aggressive adult T-cell leukemia-lymphoma: a propensity score analysis. Bone Marrow Transplant. 2019;54:1399–405.
doi: 10.1038/s41409-019-0446-z
pubmed: 30664725
Mizutani M, Takami A, Hara M, Mizuno S, Yanada M, Chou T, et al. Comparison of autologous and unrelated transplants for cytogenetically normal acute myelogenous leukemia. Biol Blood Marrow Transplant. 2017;23:1447–54.
doi: 10.1016/j.bbmt.2017.05.008
pubmed: 28533061
Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–21.
pubmed: 27276561
pmcid: 4979995
doi: 10.1056/NEJMoa1516192
Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature. 2015;518:552–5.
doi: 10.1038/nature13968
pubmed: 25487151
McNeer NA, Philip J, Geiger H, Ries RE, Lavallee VP, Walsh M, et al. Genetic mechanisms of primary chemotherapy resistance in pediatric acute myeloid leukemia. Leukemia. 2019;33:1934–43.
pubmed: 30760869
pmcid: 6687545
doi: 10.1038/s41375-019-0402-3
Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.
pubmed: 27895058
pmcid: 5291965
doi: 10.1182/blood-2016-08-733196
Sakaguchi M, Yamaguchi H, Najima Y, Usuki K, Ueki T, Oh I, et al. Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia. Blood Adv. 2018;2:2744–54.
pubmed: 30341082
pmcid: 6199656
doi: 10.1182/bloodadvances.2018020305
Bazarbachi A, Labopin M, Battipaglia G, Djabali A, Forcade E, Arcese W, et al. Allogeneic stem cell transplantation for FLT3-mutated acute myeloid leukemia: in vivo T-Cell depletion and posttransplant sorafenib maintenance improve survival. A retrospective acute leukemia working party-European society for blood and marrow transplant study. Clin Hematol Int. 2019;1:58–74.
doi: 10.2991/chi.d.190310.001
pubmed: 34595412
pmcid: 8432385
Xuan L, Wang Y, Huang F, Jiang E, Deng L, Wu B, et al. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018;124:1954–63.
doi: 10.1002/cncr.31295
pubmed: 29509276
Schlenk RF, Weber D, Fiedler W, Salih HR, Wulf G, Salwender H, et al. Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. Blood. 2019;133:840–51.
doi: 10.1182/blood-2018-08-869453
pubmed: 30563875
Yoshizato T, Nannya Y, Atsuta Y, Shiozawa Y, Iijima-Yamashita Y, Yoshida K, et al. Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. Blood. 2017;129:2347–58.
pubmed: 28223278
pmcid: 5409449
doi: 10.1182/blood-2016-12-754796
Donehower LA, Soussi T, Korkut A, Liu Y, Schultz A, Cardenas M, et al. Integrated analysis of TP53 gene and pathway alterations in the cancer genome atlas. Cell Rep. 2019;28:1370–84.
pubmed: 31365877
pmcid: 7546539
doi: 10.1016/j.celrep.2019.07.001
Hou HA, Chou WC, Kuo YY, Liu CY, Lin LI, Tseng MH, et al. TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution. Blood Cancer J. 2015;5:e331.
pubmed: 26230955
pmcid: 4526785
doi: 10.1038/bcj.2015.59
Kadia TM, Jain P, Ravandi F, Garcia-Manero G, Andreef M, Takahashi K, et al. TP53 mutations in newly diagnosed acute myeloid leukemia: clinicomolecular characteristics, response to therapy, and outcomes. Cancer. 2016;122:3484–91.
pubmed: 27463065
doi: 10.1002/cncr.30203
Rucker FG, Schlenk RF, Bullinger L, Kayser S, Teleanu V, Kett H, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119:2114–21.
doi: 10.1182/blood-2011-08-375758
pubmed: 22186996
Ciurea SO, Chilkulwar A, Saliba RM, Chen J, Rondon G, Patel KP, et al. Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations. Blood. 2018;131:2989–92.
pubmed: 29769261
pmcid: 7218750
doi: 10.1182/blood-2018-02-832360
Leung GMK, Zhang C, Ng NKL, Yang N, Lam SSY, Au CH, et al. Distinct mutation spectrum, clinical outcome and therapeutic responses of typical complex/monosomy karyotype acute myeloid leukemia carrying TP53 mutations. Am J Hematol. 2019;94:650–7.
doi: 10.1002/ajh.25469
pubmed: 30900772
Baron F, Stevens-Kroef M, Kicinski M, Meloni G, Muus P, Marie JP, et al. Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype. Haematologica. 2019;104:1168–75.
pubmed: 30523055
pmcid: 6545848
doi: 10.3324/haematol.2018.204826
Brands-Nijenhuis AV, Labopin M, Schouten HC, Volin L, Socie G, Cornelissen JJ, et al. Monosomal karyotype as an adverse prognostic factor in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem-cell transplantation in first complete remission: a retrospective survey on behalf of the ALWP of the EBMT. Haematologica. 2016;101:248–55.
pubmed: 26589909
pmcid: 4938342
doi: 10.3324/haematol.2015.132654
Oran B, Dolan M, Cao Q, Brunstein C, Warlick E, Weisdorf D. Monosomal karyotype provides better prognostic prediction after allogeneic stem cell transplantation in patients with acute myelogenous leukemia. Biol Blood Marrow Transplant. 2011;17:356–64.
doi: 10.1016/j.bbmt.2010.05.012
pubmed: 20553926
Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116:354–65.
doi: 10.1182/blood-2009-11-254441
pubmed: 20385793
Medeiros BC, Othus M, Fang M, Roulston D, Appelbaum FR. Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. Blood. 2010;116:2224–8.
pubmed: 20562328
pmcid: 3709629
doi: 10.1182/blood-2010-02-270330
Sallman DA, Komrokji R, Vaupel C, Cluzeau T, Geyer SM, McGraw KL, et al. Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes. Leukemia. 2016;30:666–73.
doi: 10.1038/leu.2015.304
pubmed: 26514544
Hamilton BK, Rybicki L, Hirsch C, Przychodzen B, Nazha A, Gerds AT, et al. Mutation clonal burden and allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant. 2019;54:1281–6.
doi: 10.1038/s41409-019-0444-1
pubmed: 30655603
Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375:2023–36.
pubmed: 27959731
pmcid: 5217532
doi: 10.1056/NEJMoa1605949
Takahashi K, Patel K, Bueso-Ramos C, Zhang J, Gumbs C, Jabbour E, et al. Clinical implications of TP53 mutations in myelodysplastic syndromes treated with hypomethylating agents. Oncotarget. 2016;7:14172–87.
pubmed: 26871476
pmcid: 4924706
doi: 10.18632/oncotarget.7290
DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19:216–28.
doi: 10.1016/S1470-2045(18)30010-X
pubmed: 29339097
Wei AH, Strickland SA Jr., Hou JZ, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II Study. J Clin Oncol. 2019;37:1277–84.
pubmed: 30892988
pmcid: 6524989
doi: 10.1200/JCO.18.01600
Sallman DA, DeZern AE, Steensma DP, Sweet KL, Cluzeau T, Sekeres MA, et al. Phase 1b/2 combination study of APR-246 and azacitidine (AZA) in patients with TP53 mutant myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Blood. 2018;132:3091.
doi: 10.1182/blood-2018-99-119990
Shouval R, Fein JA, Shouval A, Danylesko I, Shem-Tov N, Zlotnik M, et al. External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019;3:1881–90.
pubmed: 31221661
pmcid: 6595255
doi: 10.1182/bloodadvances.2019032268
Styczynski J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S, et al. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020;55:126–36.
doi: 10.1038/s41409-019-0624-z
pubmed: 31455899
Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481:506–10.
pubmed: 22237025
pmcid: 3267864
doi: 10.1038/nature10738
Cocciardi S, Dolnik A, Kapp-Schwoerer S, Rucker FG, Lux S, Blatte TJ, et al. Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation. Nat Commun. 2019;10:2031.
pubmed: 31048683
pmcid: 6497712
doi: 10.1038/s41467-019-09745-2
Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377:454–64.
pubmed: 28644114
pmcid: 5754190
doi: 10.1056/NEJMoa1614359
Roloff GW, Griffiths EA. When to obtain genomic data in acute myeloid leukemia (AML) and which mutations matter. Blood Adv. 2018;2:3070–80.
pubmed: 30425072
pmcid: 6234366
doi: 10.1182/bloodadvances.2018020206